Whole-genome sequencing reveals complex mechanisms of intrinsic resistance to BRAF inhibition.

ABSTRACT:

Background

BRAF is mutated in ∼42% of human melanomas (COSMIC. http://www.sanger.ac.uk/genetics/CGP/cosmic/) and pharmacological BRAF inhibitors such as vemurafenib and dabrafenib achieve dramatic responses in patients whose tumours harbour BRAF(V600) mutations. Objective responses occur in ∼50% of patients and disease stabilisation in a further ∼30%, but ∼20% of patients present primary or innate resistance and do not respond. Here, we investigated the underlying cause of treatment failure in a patient with BRAF mutant melanoma who presented primary resistance.

Methods

We carried out whole-genome sequencing and single nucleotide polymorphism (SNP) array analysis of five metastatic tumours from the patient. We validated mechanisms of resistance in a cell line derived from th

SUBMITTER: Turajlic S 

PROVIDER: S-EPMC3999800 | biostudies-literature | 2014 May

REPOSITORIES: biostudies-literature